Engineering integrin signaling for promoting embryonic stem cell self-renewal in a precisely defined niche

Seung Tae Lee, Jung Im Yun, Yun Suk Jo, Mayumi Mochizuki, André J. van der Vlies, Stephan Kontos, Jong Eun Ihm, Jeong M. Lim, Jeffrey A. Hubbell

Research output: Contribution to journalArticle

111 Scopus citations

Abstract

We present development and use of a 3D synthetic extracellular matrix (ECM) analog with integrin-specific adhesion ligands to characterize the microenvironmental influences in embryonic stem cell (ESC) self-renewal. Transcriptional analysis of 24 integrin subunits followed by confirmation at the translational and functional levels suggested that integrins α5β1, αvβ5, α6β1 and α9β1 play important roles in maintenance of stemness in undifferentiated mouse ESCs. Using the well-defined matrix as a tool to activate integrins α5β1 plus αvβ5, α6β1 and α9β1, individually and in combination, differential integrin activation was demonstrated to exert exquisite control over ESC fate decisions. Simultaneous ligation of these four integrin heterodimers promoted self-renewal, as evidence by prolonged SSEA-1, Oct4 and Nanog expression, and induced Akt1 kinase signaling along with translational regulation of other stemness-related genes. The biofunctional network we have designed based on this knowledge may be useful as a defined niche for regulating ESC pluripotency through selective cell-matrix interactions, and the method we present may be more generally useful for probing matrix interactions in stem cell self-renewal and differentiation.

Original languageEnglish (US)
Pages (from-to)1219-1226
Number of pages8
JournalBiomaterials
Volume31
Issue number6
DOIs
StatePublished - Feb 2010

Keywords

  • Adhesion molecule
  • Cell signaling
  • ECM (extracellular matrix)
  • Hydrogel
  • Stem cell

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

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    Lee, S. T., Yun, J. I., Jo, Y. S., Mochizuki, M., van der Vlies, A. J., Kontos, S., Ihm, J. E., Lim, J. M., & Hubbell, J. A. (2010). Engineering integrin signaling for promoting embryonic stem cell self-renewal in a precisely defined niche. Biomaterials, 31(6), 1219-1226. https://doi.org/10.1016/j.biomaterials.2009.10.054